Keck Foundation awards UF $1M to study how proteins in cells are made

The Center for NeuroGenetics at the University of Florida has received a competitive $1 million grant from the W.M. Keck Foundation to study a new idea that challenges conventional understanding of how proteins in cells are made, and their impact on inherited diseases.

Scientists have long understood the role of messenger RNA, known as mRNA, in translating instructions from DNA to make protein. Inherited diseases are caused by faulty genetic instructions, but a study led by Laura Ranum, Ph.D., director of the Center for NeuroGenetics and a professor of molecular genetics and microbiology, has introduced a new twist to the plot.

"Our research disputes the conventional dogma about what causes proteins to be expressed within cells and why," said Ranum, whose original study was done while she was at the University of Minnesota. "We discovered that proteins can be made across some repetitive disease-causing mutations in the absence of 'green light' or 'start' signals, previously thought to be required. This discovery has the potential to change the course of scientific investigation on human disease because we may have been grossly underestimating the number of proteins cells express."

Ranum specializes in the study of myotonic dystrophy - the most common form of muscular dystrophy in adults - and ataxia, a rare brain disease that robs people of their coordination and motor control. She and colleagues set out to study how proteins are made and to dig for the disease-causing genes hidden within the human genome.

A lot of DNA is made up of repetitive sequences, called genomic stuttering, said Maurice Swanson, Ph.D., the associate director of the center and a professor of molecular genetics and microbiology at the UF College of Medicine. Fifty percent of human DNA is made up of repetitive sequences, which historically have been dismissed as unimportant information, he said.

"The discovery that unusual, potentially harmful proteins are translated within these regions adds another layer to the basic biological process," said Swanson, who will help lead the new study. "The discovery leads to a whole new way of looking at disease."

Keck funding will help researchers determine how this repeat-associated non-ATG translation, or RAN translation, works, if it is a key to neurological disease and whether other repetitive sequences in the genome are translated into proteins.

"This prestigious award is significant news for the university," said UF medical Dean Michael L. Good, M.D. "It is very exciting that an influential organization such as the W.M. Keck Foundation recognizes the strength of the research program at the College of Medicine, particularly the cutting-edge expertise of Dr. Ranum and Dr. Swanson and their colleagues."

The Keck Foundation's history is to invest in scientific pursuits that have great promise, but that are outside-the-box and viewed by some as risky, Ranum said.

"We are grateful for this opportunity and excited about what we will learn," she said.

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